New European Clinical Practice Guidelines for Anal Cancer

Veronica Hackethal, MD

July 17, 2014

Three European societies have jointly issued clinical practice guidelines for the diagnosis, treatment, and follow-up of anal cancer. The guidelines were published online July 6 in the Annals of Oncology.

The new guidelines represent the first joint effort of the European Society for Medical Oncology (ESMO), the European Society of Surgical Oncology, and the European Society of Radiotherapy and Oncology, the 3 main professional societies involved in cancer care in Europe.

The anal cancer guidelines cover all aspects of this uncommon tumor, including etiology, diagnosis, risk factors, recommended therapies, and group recommendations for elderly patients, according to one of the guidelines authors and ESMO spokesperson Andrés Cervantes, MD, professor of medicine in the Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Spain.

They are "equally relevant" to medical oncologists, radiation oncologists, and surgical oncologists, Dr. Cervantes explained.

Although it is a rare disease, there are certain groups at increased risk for anal cancer, such as women, men who have sex with men, and people infected with HIV.

A history of anal intercourse increases the risk for anal cancer, as does having a large number of lifetime sexual partners, immunosuppression related to organ transplantation or medication, autoimmune disorders, social deprivation, smoking, and a history of other cancers related to human papillomavirus (HPV).

HPV is a major factor; 80% to 85% of anal cancer cases are linked to HPV. Some studies suggest that up to 80% of anal cancers could be prevented with the administration of the HPV vaccine, the authors report.

They conducted a search of Medline and PubMed for articles published from 1990 to 2013, and obtained data from 6 phase 3 randomized trials and from phase 2 randomized trials.

They guidelines provide figures and tables on tumor staging, treatment decision-making, diagnostic work-ups, and stage- and site-based treatment. They also provide an example for chemoradiation treatment, although the authors emphasize that treatment for individual patients will differ.

"Our guidelines are evidenced based. All critical statements are written with levels of evidence and grades of recommendation according to a grading system adapted from the Infectious Diseases Society of America," Dr. Cervantes reported.

"We do not think our guidelines can be seen as controversial in any way," he added, because they "do not differ much in concept from other evidence-based international guidelines."

The established standard of care, according to the authors, remains chemoradiation using combinations of 5-fluorouracil (5-FU) and other chemotherapeutic agents, mainly mitomycin C (MMC). This approach leads to "complete tumor regression in 80% to 90% of patients, with locoregional failures around 15%.... The role of surgery as a salvage treatment is accepted," they write.

Until the mid-1980s, radical surgery was the "cornerstone" of treatment," they say.

"However, following publications from the 1970s on combined modality therapy, surgery as the primary therapeutic option has generally been abandoned," Dr. Cervantes and colleagues explain. "The paradigm of external-beam radiation therapy with concurrent 5-FU and MMC developed over 30 years ago by Norman Nigro remains the standard of care."

Surgery can still be an option for well-differentiated smaller tumors (<2 cm in diameter) that have not invaded the anal margin, as long as the surgeon can attain adequate margins without affecting sphincter function, they point out.

Given the rarity of anal cancer, the guideline authors "strongly believe" that physicians should discuss clinical trial participation with patients.

They provide recommendations for supportive care, emphasizing that providers should discuss early menopause and loss of fertility with premenopausal women, and the potential for sexual dysfunction with both sexes. They also emphasize quality-of-life issues, such as stool and urinary incontinence, and the importance of pain management and palliative care.

Summary of Key Recommendations

Multidisciplinary treatment
Locoregional control is the primary aim of treatment
The optimal dose of radiation treatment is still unknown, but chemoradiation with at least 45 Gy and infused 5-FU and MMC remains the standard treatment for stage II or higher anal canal tumors; a boost with 15 to 20 Gy might be applicable, especially if chemotherapy cannot be delivered safely
For "fragile" patients with smaller tumors, less-intensive treatment might be successful, but evidence from randomized controlled trials is lacking
There is no evidence of improvement in progression-free or overall survival with neoadjuvant or adjuvant chemotherapy with cisplatin
5-FU plus cisplatin has less hematologic toxicity than 5-FU plus MMC, but outcomes and overall toxicity are similar with the 2 regimens; however, MMC is preferable because it allows for easier administration
Evaluate response from 6 weeks; data suggest that 26 weeks is optimal for evaluating complete response
During follow-up, focus on salvage if local failure occurs, which happens in less than 10% of patients over the first 3 years, and relapse is usually locoregional rather than distant
For persistent, progressive, or recurrent disease, surgical salvage should be considered; however, because techniques for anal cancer are different than those for rectal cancer, morbidity can be high


The guidelines also emphasize the importance of smoking cessation.

"Every effort should be made to ensure patients stop smoking before therapy, because smoking may worsen acute toxicity during treatment and enhance toxicity," the authors write.

Guidelines author R. Glynne-Jones, MD, from the Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom, reports receiving honoraria and/or travel support from Roche, Merck-Serono, Pfizer, Eli Lilly, and Sanofi; and receiving funding and donations of cetuximab from Merck-Serono and of bevacizumab from Roche for clinical trials. The other authors have disclosed no relevant financial relationships.

Ann Oncol. Published online July 6, 2014. Abstract


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